title: Genotype in the diagnosis of 21-hydroxylase deficiency: who should undergo CYP21A2 analysis?
abstract: OBJECTIVE
  to confirm the diagnosis of 21-hydroxylase deficiency (21-OHD) by the analysis of CYP21A2 gene in infants with clinical and/or biochemical features of 21-OHD in order to clarify which patients to submit to genetic analysis; to analyze the genotype-phenotype concordance in these infants.
  
  
  METHODS
  We studied 25 children with clinical and/or biochemical features of 21-OHD. All of them and their parents were submitted to genetic analysis of CYP21A2. Patients were classified in 3 groups according to mutations' severity: severe (group A), moderate (group B) or mild (group C).
  
  
  RESULTS
  CYP21A2 gene mutations were found in 17 children. Whereas all infants of groups A and B presented a classical form of 21- OHD, children of group C had a non-classical form of 21-OHD. Four infants resulted heterozygotes and 4 children were wildtype. A girl clinically presenting a non-classical form of 21-OHD resulted compound heterozygote with one of the mutations not described in literature (R25W) and whose residual enzymatic activity is not already known. All affected children presented a 17-OHP level after ACTH stimulation greater than 100 nmol/l. We found an optimal concordance between 17-OHP levels after ACTH test and genotype.
  
  
  CONCLUSIONS
  CYP21A2 analysis permitted to confirm the diagnosis of 21-OHD in 68% of our children. To improve this percentage we suggest to perform the CYP21A2 analysis only when 17-OHP after ACTH test is greater than 100 nmol/l. Moreover, we found an optimal genotype-phenotype concordance in the 21-OHD patients.
authors.affiliation: Pediatric Clinic, Department of Life and Reproduction Sciences, University of Verona, Piazzale Scuro 10, 37134 Verona, Italy. paolocavarzere@yahoo.it.
authors.forename: P
authors.initials: P
authors.lastname: Cavarzere
authors.forename: M
authors.initials: M
authors.lastname: Vincenzi
authors.forename: F
authors.initials: F
authors.lastname: Teofoli
authors.forename: R
authors.initials: R
authors.lastname: Gaudino
authors.forename: S
authors.initials: S
authors.lastname: Lauriola
authors.forename: E
authors.initials: E
authors.lastname: Maines
authors.forename: M
authors.initials: M
authors.lastname: Camilot
authors.forename: F
authors.initials: F
authors.lastname: Antoniazzi
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000324:Adrenocorticotropic Hormone; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase